Over 40% of women of reproductive age experience premenstrual syndrome (PMS), with 3-9% of women having severe mood and physical symptoms warranting medical treatment. In the mid 20th century, before the advent of Midol and ibuprofen, a product called Hayden's Viburnum Compound, made from Black Haw (Viburnum prunifolium L) was widely used by women to treat symptoms of PMS including cramps, anxiety and pain. Black Haw extract has been shown to have uterine spasmolytic effects in animal models, decreasing incidence of uterine cramps, possibly through binding to the GABAA receptors.5 Preliminary studies at the University of Illinois at Chicago have revealed that extracts of Viburnum prunifolium L.selectively bind to GABA/s, receptors. Therefore, it seems prudent to investigate Black Haw for the prevention of premenstrual syndrome through GABAA activity. This is a multidisciplinary, collaborative project with the focus of investigating chemical and biological mechanisms of the uterine spasmolytic activity in an extract of Black Haw. The purpose of this training grant is to educate the applicant in various pharmacology and phytochemistry techniques that have particular usefulness in the field of botanical supplements. Those techniques will be applied to determine the mechanism of GABAA activity for Viburnum prunifolium L and compare it to related Viburnum species that are often found as adulterants in a preparation of Black Haw and will include the following three aims: 1) Establish all parameters necessary for botanical authentication of Viburnum prunifolium L. and related species including the use of chemical profiling. 2) Establish a pharmacologic profile of agonist/antagonist activity of V. prunifolium stem bark extracts on the GABAA receptors. 3) Use bioassay-guided fractionation to purify the GABA-ergic principle of V. prunifolium; elucidate the structures of the isolates and verify their purity and bioactivity. The purpose of this research is to investigate the active compounds found in the botanical Black Haw (Viburnum prunifolium L.) that are responsible for reported uterine relaxant effects. Findings of this investigation will be relevant for treatments aimed at prevention of the symptoms of premenstrual syndrome. [unreadable] [unreadable] [unreadable]